title: Solution structure and peptide binding of the PTB domain from the AIDA1 postsynaptic signaling scaffolding protein.
abstract: AIDA1 links persistent chemical signaling events occurring at the neuronal synapse with global changes in gene expression. Consistent with its role as a scaffolding protein, AIDA1 is composed of several protein-protein interaction domains. Here we report the NMR structure of the carboxy terminally located phosphotyrosine binding domain (PTB) that is common to all AIDA1 splice variants. A comprehensive survey of peptides identified a consensus sequence around an NxxY motif that is shared by a number of related neuronal signaling proteins. Using peptide arrays and fluorescence based assays, we determined that the AIDA1 PTB domain binds amyloid protein precursor (APP) in a similar manner to the X11/Mint PTB domain, albeit at reduced affinity (∼10 µM) that may allow AIDA1 to effectively sample APP, as well as other protein partners in a variety of cellular contexts.
authors.affiliation: Department of Biology, York University, Toronto, Ontario, Canada.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Smirnova
authors.forename: Riya
authors.initials: R
authors.lastname: Shanbhag
authors.forename: Arwa
authors.initials: A
authors.lastname: Kurabi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mobli
authors.forename: Jamie J
authors.initials: JJ
authors.lastname: Kwan
authors.forename: Logan W
authors.initials: LW
authors.lastname: Donaldson
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D002942:Circular Dichroism; D017124:Conserved Sequence; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D040681:Structural Homology, Protein
chemical_list: C489945:ANKS1B protein, human; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D010446:Peptide Fragments